Novel or expanding current targets in fibrinolysis

Globally the leading cause of long-term disability and mortality stems from cardiovascular diseases, which creates an enormous economic burden. Currently available treatments for intravascular thrombosis consist of a large repertoire of antithrombotic agents targeting coagulation and platelet function. However, the only agents available to enhance fibrinolysis are recombinant or modified forms of plasminogen activators. Their clinical use is limited by low efficacy, life-threatening side-effects (primarily caused by the high systemic dose required) and the inapplicability for prophylactic use. This review provides an update on the latest advances in targeting the antifibrinolytic proteins, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, and will highlight novel therapeutic avenues to enhance fibrinolysis.